Specific components of the extracellular matrix (ECM) accumulate in atherosclerosis and promote[unreadable] the inflammatory phase of vascular disease. We have focused on two of these components,[unreadable] hyaluronan and versican, which interact with each other to form higher ordered molecular[unreadable] complexes and not only contribute to ECM expansion during the development of vascular disease[unreadable] but also have a dramatic effect influencing the phenotype of arterial smooth muscle cells. Recently,[unreadable] we found that an ECM enriched in hyaluronan and versican promotes the adhesion of monocytes in[unreadable] a hyaluronan dependent manner suggesting that these specific ECM components may form part of[unreadable] what could be considered a pro-inflammatory ECM. These observations have led us to hypothesize[unreadable] that hyaluronan and versican are produced by vascular cells in response to specific inflammatory[unreadable] stimuli and contribute to the formation of an ECM that binds monocytes. We further hypothesize[unreadable] that monocyte/macrophage also synthesize these ECM components in response to inflammatory[unreadable] stimuli and degrade hyaluronan and versican and that a balance between these two activities[unreadable] partially regulates the phenotype of the monocyte/macrophage. To test this hypothesis, we will[unreadable] have 4 specific Aims. In Aim 1, we will identify the full nature of this specialized ECM and test the[unreadable] requirements for these components for these components in hyaluronan-dependent monocyte[unreadable] adhesion. In Aim 2, we will explore the role that hyperlipidemia and modified lipids play in the[unreadable] generation of this ECM and define the changes in versican and hyaluronan during the development[unreadable] of atherosclerosis. Aim 3 will focus on the synthesis and degradation of versican and hyaluronan[unreadable] by the monocyte/macrophage and the impact of these ECM components monocyte/macrophage[unreadable] proliferation, adhesion and migration. In Aim 4, we will test the importance of this hyaluronan based[unreadable] ECM in the generation of both early and late atherosclerotic lesions by using mouse models of[unreadable] atherosclerosis susceptibility and animals in which specific genes required for the assembly of this[unreadable] ECM have been ablated.